Date of Award

January 2016

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Yong Zhu

Abstract

Background: Lung cancer is the most frequently diagnosed cancer and one of the top cause of cancer death worldwide. The recent discovery of PIWI-interacting RNAs (piRNAs), one type of non-coding RNAs, has been shown to be involved in tumorgenesis pathways of various types of cancer types by accumulating evidences. However, the role of piRNAs in lung cancer development is underexplored.

Methods: Genotype and phenotype data were obtained from a genome-wide association study of lung cancer risk (3,702 cases and 3,739 controls) and 1,173 imputed piRNAs variants were analyzed by association analysis for lung cancer risk. A secondary expression analysis is also performed for 200 piRNAs to compare their expression levels in 497 lung adenocarcinoma patients versus 46 normal controls. Following in vitro functional analysis was also performed for the piRNAs variants identified from the association analysis.

Results: In the association analysis, one SNP (rs1169347) which can be mapped to two piRNAs (piR-5247 and piR-5671) was identified as statistically significantly associated with lung caner risk (FDR P-value <0.05). In the following functional analysis, results from cell viability assay showed a cell-growth-promoting effect of the major allele of the identified SNP. In the secondary expression analysis, 5 piRNAs were found significantly over-expressed in lung adenocarcinoma patients.

Conclusions: This comprehensive post-GWAS study provided important evidences for the role of piRNAs in lung cancer development through either their own functions or interactions with other protein-coding genes.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 06/07/2018

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